Race-Based Drugs

[CDarwin]

There was an article about BiDil, the "race-based" drug for congestive heart failure in in August's Scientific American.

 

What are some opinions on the concept of race-based medicines? Personally, I think it's a terrible idea. It's supposed to be part of pharmacogenetics, medicines tailored to a person's specific genome, which is fine, but race is a horrid proxy for genetics. Race is a concept with genetic factors, but more importantly cultural and historical ones. If 20th century anthropology has produced anything, that realization is it. The story behind BiDil isn't encouraging either, but that's anecdotal. We should be highly skeptical of drugs of this sort even with more legitimate origins.

[ecoli]

First you need to accept that different 'races' have slightly different genetics associated with them.

 

If come drug help black people more then white people, and a slightly different drug helps white people more than black people, why would we deny people access to the best health care for them, just to be politically correct. That's just practicing bad health care.

 

Yes, there are historically and cultural implications when considering race... but science is not terribly interested in that. And if we can make better drugs on the basis of race, and thereby save more lives... then it's worth it.

 

And, anyway, race is just a product of ancestral location. Would it make you more comfortable to discriminate the medicine based on "african vs. european vs. asian ancestry"? It's all the same thing to science.

[Sisyphus]

Obviously whatever works, works, and so I agree with ecoli. However, it was also my understanding that, genetically, the "races" for which you could show such overall tendencies don't necessarily correspond to what are culturally recognized as races. For example, there is more variation among black people than in everyone else combined. (That's a hypothetical and I don't know if it's true, but I seem to remember something like that.) So considering "race" in terms of genetic groups in assessing the chances a particular drug will work is a good idea, but unfortunately "race" in terms of cultural groups is a quite crude approximation of that. But still, I guess a crude approximation is better than intentional blindness, right?

[insane_alien]

whether the PC brigade like it or not, there are some physiological differences(they are not good or bad but simply evolved traits due to differeing enviroments when we did not have quick and easy travel to the rest of the globe) for instance, people with really dark skin do not produce as much vitamin D and there are a few other small differences.

 

normally these differences are unnoticeable but they can affect the chain of reactions a drug which can affect the potency of the drug.

 

you could even take this down to individual body chemistry. some people are affected by drugs more than others. if we had the technical know how and resources, we would taylor drugs to suit the individual.

[Dak]

However, it was also my understanding that, genetically, the "races" for which you could show such overall tendencies don't necessarily correspond to what are culturally recognized as races.

 

it's a tad complicated, but genetically valid races often corrispond with what's culturally considered a race. eg, 'black' isn't a race, but 'negro' is a valid genetic race.

 

----

 

whenever the distribution of a medically relivent allele corrisponds with a visually-discernable race, i don't see what the problem is with capitalising on that fact. eg, the drug in question iirc works only if you have a certain receptor on your heart, which is usually only found in negros. no point in giving that drug to caucasians and mongaloids, nor in denying negroes it 'just to be fair'

 

african vs. european vs. asian ancestry

 

I think your third group should be orientals + misc. asians are cacasian, same as europeans... i think.

[CDarwin]

First you need to accept that different 'races' have slightly different genetics associated with them.[/Quote]

 

But "race" is a poor proxy for those genetics. Look at the genes and the traits, not at the "race".

 

If come drug help black people more then white people, and a slightly different drug helps white people more than black people, why would we deny people access to the best health care for them, just to be politically correct. That's just practicing bad health care.

 

I doubt that a drug could really be made that would help only one "race" but not any other. The "race" we decided to call "black" isn't so genetically homogeneous that a drug can be tailored to suit only "blacks" and not work for many "whites" and "Asians" as well. BiDil is a good example of that. When you make a "race-specific" drug, you're just excluding people who the drug could potentially help.

 

Yes, there are historically and cultural implications when considering race... but science is not terribly interested in that. And if we can make better drugs on the basis of race, and thereby save more lives... then it's worth it.

 

But I doubt that's possible, because you're working with a concept that's basically biological fictional.

 

And, anyway, race is just a product of ancestral location. Would it make you more comfortable to discriminate the medicine based on "african vs. european vs. asian ancestry"? It's all the same thing to science.

 

And it would be just as much a waste of time. Humans have interbred like crazy. The average "African-American", for example is 1/5 "European." How "African" would you have to be for an "African" drug to work for you?

 

See "Racing around, getting nowhere" from the October 2005 issue of Evolutionary Anthropology.

 

it's a tad complicated, but genetically valid races often corrispond with what's culturally considered a race. eg, 'black' isn't a race, but 'negro' is a valid genetic race.

 

Erm.. no. They're both pretty much made up. Variation exists, absolutely, but it exists in a continuum. Cultures arbitrarily decide where to draw lines through this continuum and make "races." Now we're trying to take those arbitrary lines and make medicines with them, and it's counter-productive because it's the variation that matters.

[Sisyphus]

 

But "race" is a poor proxy for those genetics. Look at the genes, not a the "race".

 

An imperfect proxy, obviously, but not a useless one.

 

I doubt that a drug could really be made that would help only one "race" but not any other.

 

But that's not the point, is it? It's not that these drugs can only help a particular race, but that statistically they work better for a particular race. And so taking race into account could make the difference between whether one or another drug is more likely to be effective.

 

But I doubt that's possible, because you're working with a concept that's basically biological fictional.

 

But it is possible, because it's been demonstrated.

 

And it would be just as much a waste of time. Humans have interbred like crazy. The average "Africa-American", for example is 1/5 "Caucasian." How "black" would you have to be for a "black" drug to work for you?

 

Again, it's not drugs that only work for a black person. It's drugs that, statistically, are more likely to work better for a black person.

[CDarwin]

An imperfect proxy, obviously, but not a useless one.[/Quote]

 

But why not use better ones, like a person's actual physical and medical history? Take drugs for sickle-cell anemia. Obviously, those drugs are going to

help more people from West Africa than they there are people from Norway, but it's not being from West Africa that matters; it's having sickle-cell anemia.

 

But that's not the point, is it? It's not that these drugs can only help a particular race, but that statistically they work better for a particular race. And so taking race into account could make the difference between whether one or another drug is more likely to be effective.

 

I can see the validity of that argument, although there are certainly problems there too. What works frequently in people from Nigeria might be completely different than what works most commonly in people from Ethiopia. Again, the cultural construct of "race" is an impotent proxy for the truly useful information, and by focusing on it we risk missing what's really important. I guess that's what I'm getting at.

 

But it is possible, because it's been demonstrated.

 

Where?

[Tearfeather]

But "race" is a poor proxy for those genetics. Look at the genes and the traits, not at the "race".

 

For a long time already, scientists and MD doctors are trying to find the ''formula'' that would help them to decide exact drug dosage for each patients.

I agree with what you said that the best way is to look at patients genes, BUT as you know we live in capitalistic world and genes tests costs a lot of money, moreover they take a lot of time wich usually patient doesn't have...so, genes examination is good in CSI movies, but unfortunately in real life we have to find cheeper and faster ways.

[CDarwin]

Maybe here's another way to approach the question: If assuming a person's genetics based on what your society calls their "race" and prescribing them certain drugs accordingly helps 50% of your patients but hurts 30%, is it worth it? Since we've already established that "race" is imperfect, might relying on it do almost as much harm as good due to how complex the relationship between ethnicity and genetics is?

[pioneer]

Tailoring drugs to race is the first logical step toward tailoring drugs to the individual. There is no one medicine, which works as affectively, and at the same dose, for all people. The current approach makes, a one size fits all, with the hope that everyone is a size 10. But there are all sizes. The same is true for laws against controlled substances which are shown to adversely affect health. Law is also metered out, as a one size fits all, rather than a spectrum, where risks assessments are characterized to the individual.

 

From a practical point of view, there are two social forces that make the ideal, of tailored medicine and tailored prohibiiton, much more difficult. Political correctness is one social force, that pitches one size fits all. One is not allowed to focus on differences, but needs to assume uniformity. For the good stuff we are all the same. For the bad stuff we are all the same. The paradox is, if we are all the same, why do only certain people make these decisions for all. Doesn't that imply that difference exist?

 

The other social force is, statistical research is very cumbersome. Because it can lead to conflicting studies or allows fixing the game, FDA approval often takes years, until the slight of hand is sufficiently filtered out. So if we made a skin medicine, tailored to Mary, it would takes years to get to her and would end up costing about $10M for a 4oz jar. The state of the art needs to upgrade to rational approach, that can speed up the entire process. Statistical medicine is just too expensive to implement beyond a one size fits all approach, without esculating the costs of medical care.

[John Cuthber]

Just a thought. Is having drugs tailored to racial characteristics morally different from having drugs tailored to the sexes?

I grant that it's generally more difficult to establish the racial traits than sex, but if that distinction can be made then what's the problem?

[ecoli]

But "race" is a poor proxy for those genetics. Look at the genes and the traits, not at the "race".

 

Racial characteristics are a phenotypic expression of the genetype. Just like genetics diseases or genetic propensity to be at risk for certain diseases. If there is a particular disease propensity (that is probability, mind, not racism)associated with a specific disease (as has been scientifically determined) then why not tailor drugs specifically for those people?

 

Biotechnology is good, but every doctor can't necesarily "look up" an indivdual's genome in the doctor's office. It would be great if we had access to the individual's genome, and if we understood genetics well enough to determine, quanititatively, exactly what the individuals risk to genetic disease would be.

 

But, obviously, there are technical, physical, and even moral considerations behind this, and we're not technologically there yet anyway.

 

Wouldn't it be great if there was some way we could generalize people into different catagories based on their genetic ancestoral history, in which we can make inferences based on individuals we can study the genetics of, and then apply that to other people in the group?

 

Oh wait... we can do that based on race!

I doubt that a drug could really be made that would help only one "race" but not any other. The "race" we decided to call "black" isn't so genetically homogeneous that a drug can be tailored to suit only "blacks" and not work for many "whites" and "Asians" as well. BiDil is a good example of that. When you make a "race-specific" drug, you're just excluding people who the drug could potentially help.

That is an incorrect interpretation of what race-based drugs try to do.

 

A drug tailored to a specific race is done so because that race as a variation in the expression of the disease that must be fought in a way slightly different then another race. The goal is NOT to exclude certain races from getting medication - usually a member from another race can use the drug targetted it to a different race, it just won't work optimally. The goal is to optimize the quality of treatment, keeping mind things such as genetic variation as a result of racial differences. In evolutionary terms, that's intepreted as; different environmental pressures caused humans genetics to vary, and express optimal phenotypic characteristics in their ancestoral location. In some cases, this changed risks and how different people are able deal with various diseases.

 

That's why African american slaves were so useful in the carribean, because the indigenous people were very vulnerable to smallpox, but the africans were almost all immune to it.

If you were to translate this into a pseudo-present day scenario, you wouldn't deny treatment to native americans, because the africans are immune!!

If anything, to ignore the racial differences would be racist.

 

And to only consider dispensing drugs on an individual, case-by-case basis, is uneconomical and a waste of time... especially when it's perfectly fine to generalize based on race.

 

And it would be just as much a waste of time. Humans have interbred like crazy. The average "African-American", for example is 1/5 "European." How "African" would you have to be for an "African" drug to work for you?

 

This is true... we are getting more 'inbred.' But I'm not so sure racial boundries are blurring so fast that race-based drugs are completely useless. A stat-based study would be nice for this though. Also, a study that tells us (if any) traits that cause genetic diseases dominate based on "inter-racial coupling." Of course, that may cause some of it's own moral indignation in it's own right.

 

Erm.. no. They're both pretty much made up. Variation exists, absolutely, but it exists in a continuum. Cultures arbitrarily decide where to draw lines through this continuum and make "races." Now we're trying to take those arbitrary lines and make medicines with them, and it's counter-productive because it's the variation that matters.

perhaps you're right, but I think that's also oversimplifying things. I don't think there's any way to be sure where there are stict racial boundries or a continuum. Either way, it would be a difficult measure to quantify... based on physical biological properties. And especially hard to do in present day's migration patterns.

[Revenged]

I'm not sure some people understand fully...

 

The underlying problem was created because the FDA only approved BiDil for blacks in 2005... You legally cannot prescribe BiDil to whites in america...

 

However, the two generic drugs within BiDil are prescribed separately to whites - but you cannot give them in combination... {e.g. isosorbibe dinitrate is a simple vasodilator to treat angina... hydralazine is an anti-hypertensive and reduces blood pressure (also by vasodilator)...}

 

The apparent reason that the combination of the two is only prescribed to blacks is not because they work better on blacks than whites (which is what many of you are implying)... The fast majority, if not all, of white people with heart failure are also taking vasodilator drugs and if anything they work better in white people...

 

The reason they are given is that other standard treatments, such as ACE inhibitors, don't work as well in blacks and so they are given an alternative (e.g. in America - BiDil)...

 

It's that simple... In my opinion the FDA should have just approved the drugs for everyone since they can be prescribed separately... and then this problem wouldn't have occurred...

[CDarwin]

Tailoring drugs to race is the first logical step toward tailoring drugs to the individual. There is no one medicine, which works as affectively, and at the same dose, for all people. The current approach makes, a one size fits all, with the hope that everyone is a size 10. But there are all sizes. The same is true for laws against controlled substances which are shown to adversely affect health. Law is also metered out, as a one size fits all, rather than a spectrum, where risks assessments are characterized to the individual.

 

Quite to the contrary, race-based drugs threaten to lead to "one-size fits all" medicine. "Here Mrs. Okigawa, have some Asiasprin. You need Scotsocil Mr. Smith!" There is more variation among members of a 'race' than between 'races.' By looking at race as a defining factor you just pigeon-hole people to a physiological stereotype that's potentially much more harmful than the general assumptions doctors make on the basis of health, sex, etc.

 

Just a thought. Is having drugs tailored to racial characteristics morally different from having drugs tailored to the sexes?

I grant that it's generally more difficult to establish the racial traits than sex, but if that distinction can be made then what's the problem?

 

We're not talking about morality, we're talking about efficacy. I don't know why everyone seems so bent on painting this as "PC vs good science." "Race" is bad science.

 

Racial characteristics are a phenotypic expression of the genetype. Just like genetics diseases or genetic propensity to be at risk for certain diseases. If there is a particular disease propensity (that is probability, mind, not racism)associated with a specific disease (as has been scientifically determined) then why not tailor drugs specifically for those people?

 

That's not what I'm talking about. Obviously, sickle-cell drugs are going to benefit mostly "black" people. What I'm talking about is using resources to make one heart drug for "black" people and one heart drug for "white" people when it's extremely unlikely that either drug would be very much more effective in either group than it would in the other and that by tagging the drug with a race you potentially deny it to the people who might need it.

 

That's why African american slaves were so useful in the carribean, because the indigenous people were very vulnerable to smallpox, but the africans were almost all immune to it.

If you were to translate this into a pseudo-present day scenario, you wouldn't deny treatment to native americans, because the africans are immune!!

If anything, to ignore the racial differences would be racist.

 

Again, not what I'm talking about. You also wouldn't say that small-pox drugs only work on Native Americans so we're not going to give them to the stray African who gets smallpox, either, and that's more analogous to associating drugs with race.

 

A drug tailored to a specific race is done so because that race as a variation in the expression of the disease that must be fought in a way slightly different then another race. The goal is NOT to exclude certain races from getting medication - usually a member from another race can use the drug targetted it to a different race, it just won't work optimally. The goal is to optimize the quality of treatment, keeping mind things such as genetic variation as a result of racial differences. In evolutionary terms, that's intepreted as; different environmental pressures caused humans genetics to vary, and express optimal phenotypic characteristics in their ancestoral location. In some cases, this changed risks and how different people are able deal with various diseases.

 

That's a nice idea, but I've yet to see a single example of where that's been the case, and from what I know about "race" and how flimsy of a concept it is I doubt it ever will be. There's just so much more individual variation than "racial" variation, and "race" is just so tied to non-biological factors. That's my thesis, I suppose. I'm not saying that racial drugs are impossible, and if they'd work, fine; I'm just exceedingly skeptical.

[Dak]

It's that simple... In my opinion the FDA should have just approved the drugs for everyone since they can be prescribed separately... and then this problem wouldn't have occurred...

 

why approve a drug with inherent risks for a group that has no need for it?

 

It'd be like approving the contraseptive pill for use in males... they don't need it, ergo it's not worth any risks, so I wouldn't be surprised if you're not allowed to prescribe it to males.

[foodchain]

Race is a flimsy concept. What is the true genetic variation of Germany to Poland by chance, and does any particular phenotypic concentration reflect anything that has to do with such? I mean the human genome is just that, or else needing corrective eyewear is racially what? I mean do we make drugs for say a particular tribe of people, or even a state? Personally I can only see such drugs working for outstanding traits, such as sickle cell, not a "race". That term has about as much meaning really in science as saying gravity does not exist. I mean I can breed with any female of any race right? So what’s that say about the human genome.

 

Its targeted product placement, not science. Saying something genetic is racial should mean I cant ever get it, nor could any offspring I could produce with any “race”, and lastly racial differences are super flimsy compared to the biological difference, or dimorphism between sexes.

[Dak]

Its targeted product placement, not science. Saying something genetic is racial should mean I cant ever get it, nor could any offspring I could produce with any “race”

 

no it doesn't, it just means that it's much more/less common in one race than another. for example, iirc blood type B is reeeeeally uncommon in native americans, but quite common in other 'races'. tada, a medically relevent race-based genetic difference. doesn't work with all alleles, obviously, but with some it does.

 

and lastly racial differences are super flimsy compared to the biological difference, or dimorphism between sexes.

 

Generally that's true, and often the distribution of an allele completely disreguards ethnic/racial boundries. however, it often doesn't, and is distributed along ethnic/racial lines.

 

when that's the case, it allows for racially-targetted medisine.

[Revenged]

why approve a drug with inherent risks for a group that has no need for it?

 

It'd be like approving the contraseptive pill for use in males... they don't need it, ergo it's not worth any risks, so I wouldn't be surprised if you're not allowed to prescribe it to males.

 

No, it isn't like that... Vasodilators are used to treat everyone of all race for heart failure... It's just that the combination of vasodilators used in BiDil isn't...

[CharonY]

Actually one would eventually need to do proper genotyping before proceeding much further.

As the genetic variation among native africans is higher than in any other ethnic group I doubt that there are many markers that can be simply associated to something fuzzy as "negro". Also, I wonder how the variability among African-Americans is as compared to native Africans (as I think the drug in question was tested in the USA?).

[Bornsatin]

I'm not too sure but if I had to guess, I'd say different races have developed different resistance and immunity towards drugs, considering that the concept of race-based drugs isn't all that wrong. The idea does sound a little suspicious x(

[pioneer]

The environment affects the types of genetic changes which will give one selective advantage. For example, although growing thick fur is good for a cold climate, this genetic change is counterproductive at the equator. What could give an animal selective advantage in one environment could be a selective disadvantage in a different environment. Long skinny legs may be good for wading in marshes to catch fish, but it not good in the mountains. Long antlers in the plains, may pose a problem in the thick jungle. The environment will set the standard, with respect to the range of possible genetic changes, that will be affective in that environment.

 

Relative to the various races, each sort of evolved in an eco-system. What was useful under those conditions may or may not be optimum in a different eco-system. The standard now is western culture. One is sort of taking people from the equator, plains, mountains, valleys, rivers, oceans, etc., and putting them all in an auditorium environment. A good example, were the native Americans before the Europeans came. They never were exposed to smallpox. The Europeans had already did the adaptation dance. The native Americans never had any environmental reason to adapt so they were ill prepared when small pox came. If we alterred the environment where we homogenize, the problems shift to another race. Knowing where adaptation occurred and the new environment allows us to anticipate the types of medicines one may need to take.

 

The problem is not objective but is subjective due to liberalism. To target the needs of a non-indigenous race, implies races are different. But the liberal pitch is we are all the same. So there is a tendancy to enforce this subjective premise at the expense of objectivity. There is room for only one sherif in town, with subjectivity usually the political winner.

 

A good analogy is a polar bear living in Texas. His fur was his selective advantage in the arctic. We work under the assumption that all selective advantage is exactly the same. But in reality, he may be better off shared in Texas, to make him cooler. But if we do that, now he looks a little different. So people will resist shaving him, but prefer that he deal with the heat, so they can feel better out the polar bear's selective advantage. Current evolutionary theory reinforces this since it doesn't give enough weight to the environment setting the standard for selective advantage.

[michael]

Pharmacogenetics (sic) or Pharmacogenomics has the potential to save thousands of lives.

Also to save billions in health care costs.

People all react differently to drugs. Part of this is due to genetic difference

The concept of "race" probably just confuses the issue.

"Race" is a word with a lot of emotive baggage.

It is probably better just to say some people die if given Warfarin other people get better if given Warfarin.

 

 

Tests are being developed to help predict the euphemistically called, "Adverse Drug Reactions" (ADRs) one of the most common reasons for people to see a doctor or die.

 

What is Pharmacogenomics (PGx)?(from Healthscope's advertising brocure to Oz GPs)

 

Pharmacogenomics (PGx) is the science of how a person’s genetic make-up influences the way we respond (either positively or negatively) to drugs.

 

We all know examples where some people treated with medication either respond well, while others do not respond at all, while others experience some serious adverse reaction to the medication.

The current paradigm for treating patients with medication is “one size fits all” or as in some cases, medication is based on ’trial and error’.

 

Variable inter-individual responses to certain drugs can be influenced by a number of factors, eg age, sex, pathology, life style or co-medication.However, it is becoming more evident that genetics plays a central role.

In some instances genetics accounts for up to 60% of the patient variation in responses to drugs.

 

Pharmacogenomics identifies individuals who are at high risk of experiencing adverse drug reactions or those who may not respond to certain medications.

 

Pharmacogenomics is the first step toward ’personalised medication’.

What is PGx Testing?

 

PGx DNA tests look for changes in genes that play a major role in either:

 

1. Drug Clearance

 

Depending upon ethnicity, between 10-25% of the population are genetically known as “poor metabolisers”, that is they do not have the enzymes within their livers to clear specific drugs from their bodies.

As such, they are at increased risk of adverse drug reaction when blood concentrations of drugs increase to toxic level.These individuals require either alternate medication or much lower doses of the drug.

 

On the other hand, between 5-25% of the population are genetically known as “ultra metabolisers”, that is they have multiple copies of genes that code for drug clearing enzymes.Here, these individuals clear the drug so fast that they usually have no effect, therefore require much higher doses than normal.

 

2. Drug Transport & Action

 

Other genes code for either the drug transporter or drug receptor.

Here individuals with genetic variants may not be able to respond to medication since the level of receptor has changed or it is no longer functioning.

 

Why Is PGx Important Today?

 

Adverse Drug Reactions (ADR):

 

USA

 

* 2.2 million adverse drug reactions per year.

* 4th – 6th leading cause of death.

* Cost of drug related morbidity and mortality $170 billion.

* ADR’s account for 5% of all hospital admissions.

* Overall incidence of serious ADR’s is 7%.

 

UK

 

* 250,000 people per year admitted to hospital with an ADR.

* 6.5% of new hospital admissions

* Estimated healthcare burden of ADRs, over £450 million.

 

Australia

* 140,000 ADR’s reported each year.

* One in ten GP consultations are patients who have suffered anADR.

 

 

CYP2C19metabolises 15% of all prescribed drugs.

It is absent in 20-30% of Asians and 13% of Caucasians.

 

A bit (but not a lot) more info here:

Healthscope Molecular News

Healthscope is a firm that is setting itself up to do the genetic tests required to reduce or eliminate ADRs

[Psyber]

One pathology service here in Melbourne is offering a short form of profiling of enzyme systems in the liver from blood sampling, which may help to select the right medication for a particular patient based on knowledge of this genetically shaped aspect of metabolism. You can select the product they are not going to metabolise rapidly.

 

However, it is of limited usefulness in real practice, and about AU$450.00 for the screen, which most people could not afford.

[vampares]

I'm on the pill, my sister smokes crack. If I had a black friend or little step-brother I teach him to Dust-Off and go Robo-tripping in the 'hood.

 

I'd heard of certain heart failures that occur in mulattoes (it was in this context -- that blacks don't have heart failures like this ordinarily). I'm not sure how this comes about -- if it's cause their mixed or if it's because of something else (like the mini-thin's I've been selling them).

 

Maybe I ought to reconcider my pharmacopoeia. Thanks for the heads up! We're off to the clinic!

 

I'm not too sure but if I had to guess, I'd say different races have developed different resistance and immunity towards drugs, considering that the concept of race-based drugs isn't all that wrong. The idea does sound a little suspicious x(

 

Now that I'm sniffing glue again, the idea is a little weird.

 

How about drugs for a certain class of people? Like the lower-middle class of people. Or business people who get stuck in traffic a lot? Where are the drugs for fat people? Banned because they cause heart attacks. It's tough to get around that whole stigmata thing.